Date of Award

2017

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Materials Science & Engineering

First Advisor

Vivek B. Shenoy

Abstract

Understanding the mechanism of the load bearing and force transmission throughout fibrous biological structures can help decode complex physiological and pathological phenomena and provide insight into possible therapeutic solutions. Fibrous structures are characterized by one-dimensional fibers stabilized by cross-linking proteins and molecules. Preferentially aligned fibers form well-organized parallel bundles, whereas randomly distributed fibers create isotropic three-dimensional networks. Tendons, composed of staggered arrangements of collagen fibrils, and axonal cytoskeleton in neurons, composed of alternate rows of microtubules, are two instances of structures with aligned fibers. Collagen fibrous networks which make up the extracellular matrix (ECM) of connective tissues are an example of fibrous structures with random orientation of the fibers. As fibrous structures respond to external stresses, cross-linking elements transfer the loads between the fibers and transmit the bulk deformations from one end of the structure to the other end. This mechanical machinery allows these structures to sustain large deformations and transfer tissue scale forces to the subcellular level. In this thesis, we quantify the influence of this mechanism on several physiological and pathological processes related to tendons, axons, and ECMs. First, we employ the shear-lag model (SLM) to quantitatively identify the key parameters affecting the mechanical behavior of fibrous materials. Next, by extending the SLM and including poroelastic effects, we study the movement of the interstitial fluid throughout fibrous tissues. Notably, our model explains the exudation of fluid from tendon structures in response to tensile stretching, in agreement with previous observations. By incorporating the dynamics of the engagement of the cross-links in the load transfer pathway, we elucidate the underlying mechanism of viscoelastic behavior of fibrous tissues. In particular, the rate-dependent vulnerability of axons to dynamic loadings during brain injury is modeled and validated with previous in vitro studies. Finally, we study the nonlinear elasticity induced by the realignment and reorganization of the collagen fibers in the ECM and examine its impact on regulating cell-matrix interactions. Notably, our model shows that mechanical principles mediated by the ECM nonlinearity and the contractility of the cells play a crucial role in determining the phenotype of the tumor cells.

Files over 3MB may be slow to open. For best results, right-click and select "save as..."

Share

COinS